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Cytoplasmic Ribonucleoprotein Foci in Eukaryotes: Hotspots of Bio(chemical)Diversity.

Layana C, Ferrero P, Rivera-Pomar R - Comp. Funct. Genomics (2012)

Bottom Line: They involve the regulation of the metabolism of mRNA in cytoplasmic foci.A challenging prospective is to know how many different classes of foci exist, which functions they support, how are they formed, and how do they relate one to each other.Here, we present an update of the component of the different granules, a possible function, and hypothesis on their in vivo dynamics related to translational control.

View Article: PubMed Central - PubMed

Affiliation: Centro Regional de Estudios Genómicos, Universidad Nacional de La Plata, CP 1888 Florencio Varela, Argentina.

ABSTRACT
The life of an mRNA from transcription to degradation offers multiple control check points that regulate gene expression. Transcription, splicing, and translation have been widely studied for many years; however, in recent years, new layers of posttranscriptional and posttranslational control have been uncovered. They involve the regulation of the metabolism of mRNA in cytoplasmic foci. They are collections of ribonucleoprotein complexes that, in most cases, remain still uncharacterized, except the processing bodies (PBs) and stress granules (SGs), which have been studied (and reviewed) in detail. A challenging prospective is to know how many different classes of foci exist, which functions they support, how are they formed, and how do they relate one to each other. Here, we present an update of the component of the different granules, a possible function, and hypothesis on their in vivo dynamics related to translational control.

No MeSH data available.


Relationship among active polysomes and PBs. The recruitment of active polysomes to PB implies the removal from the mRNA of the translation factors by translational repressors. Some of them have been demonstrated to interact with eIF4E in vivo (rck/p54 and eIF4E-T, [16]). They further interact and/or recruit the enhancers of decapping Lsm1-7 or the miRNA-related protein GW182 to form the PB. Later on, they assemble the decapping and degradation enzymes and/or the proteins required for silencing and storage into PB. All the intermediate steps of this process can represent different populations of granules coexisting in the cell and visible with different morphology that might reflect a variety of components and/or diverse stoichiometry.
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fig2: Relationship among active polysomes and PBs. The recruitment of active polysomes to PB implies the removal from the mRNA of the translation factors by translational repressors. Some of them have been demonstrated to interact with eIF4E in vivo (rck/p54 and eIF4E-T, [16]). They further interact and/or recruit the enhancers of decapping Lsm1-7 or the miRNA-related protein GW182 to form the PB. Later on, they assemble the decapping and degradation enzymes and/or the proteins required for silencing and storage into PB. All the intermediate steps of this process can represent different populations of granules coexisting in the cell and visible with different morphology that might reflect a variety of components and/or diverse stoichiometry.

Mentions: From the previous analysis, one can establish many unsolved aspects on cytoplasmic foci function. One of them is the dynamic of the mRNP remodeling. The current model suggests an active movement of mRNPs from and to polysomes and from and to SG and PB [33]. However, how does it happen and the factors involved are not known. Translationally active mRNAs can interact, in response to errors in translational initiation or to specific recruitment of regulatory proteins, with translational repressors such as Dhh1, Pat 1, Lsm1-7, eIF4E-T. Those factors would promote the replacement of the translational machinery from the mRNA, promote the cap removal and determine degradation [33] or the accumulation of silenced mRNA in PB. Within PB, mRNPs could undergo further remodeling and define a path to follow, including their return to polysomes. In addition, PBs have been shown to interact and exchange components or their own nature with SG (reviewed in [6, 7]) in a process that may result in mRNPs intermediates of unknown nature. Evidence for the diversity of cytoplasmic foci and their components results from immunocytochemistry and colocalization studies. A common factor present in most cytoplasmic mRNPs is the cap-binding protein eIF4E. eIF4E occurs in active polysomes as a translation initiation factor, in SG as part of the stalled initiation complex, and in PB as the only translation factor present there in multicellular eukaryotes. We observed in Drosophila S2 cells that eIF4E colocalizes with different pairs of markers, either for PB (GW182, Lsm1, Me31B—an ortholog of the helicase rck/p54) or SG (TIA-1) and that the colocalization does not occur in all foci in the same way (PVF, CL, and RRP, unpublished data and Figure 1). In some cases, the foci contain one, the other, or both components. In the foci that show colocalization of both factors, the relative amount of each component may vary from foci to foci, as judged by confocal microscopy quantification of the colocalized factors (PVF, CL, RRP, unpublished observation). This implies that there are a diversity of granules. An appealing hypothesis is that eIF4E is a common link among different mRNPs, playing different roles depending on their interactors. One plausible function could be that the accumulation of mRNPs in eIF4E-containing foci is a way to regulate the rate of translation in different physiological states (cell cycle phases, developmental stages, circadian rhythms). Moreover, it has been reported that, in mammalian cells, eIF4E interacts in PB with at least two factors, rck/p54 and eIF4E-T [21]. These are simultaneous interactions within the PB and imply that both proteins could contact different domains of the same eIF4E molecule or that they would represent different populations of mRNPs or different functions within the same PB. In either cases, the complexity of the interactions in vivo is more diverse than it has been expected. A model for the remodeling of active mRNPs to silence and degradation based on Andrei et al. [21] is depicted in Figure 2. This might require several intermediate states that can be the maturation steps of a mRNA in the way of a PB or within a PB. This would correlate with the large diversity of components and interactions within a cytoplasmic foci and the diversity of the foci within a cell. The understanding of the dynamics of mRNP is far from clear and unpredictable paths remain to be discovered. They will need further research and more sophisticated methods for in vivo studies.


Cytoplasmic Ribonucleoprotein Foci in Eukaryotes: Hotspots of Bio(chemical)Diversity.

Layana C, Ferrero P, Rivera-Pomar R - Comp. Funct. Genomics (2012)

Relationship among active polysomes and PBs. The recruitment of active polysomes to PB implies the removal from the mRNA of the translation factors by translational repressors. Some of them have been demonstrated to interact with eIF4E in vivo (rck/p54 and eIF4E-T, [16]). They further interact and/or recruit the enhancers of decapping Lsm1-7 or the miRNA-related protein GW182 to form the PB. Later on, they assemble the decapping and degradation enzymes and/or the proteins required for silencing and storage into PB. All the intermediate steps of this process can represent different populations of granules coexisting in the cell and visible with different morphology that might reflect a variety of components and/or diverse stoichiometry.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368187&req=5

fig2: Relationship among active polysomes and PBs. The recruitment of active polysomes to PB implies the removal from the mRNA of the translation factors by translational repressors. Some of them have been demonstrated to interact with eIF4E in vivo (rck/p54 and eIF4E-T, [16]). They further interact and/or recruit the enhancers of decapping Lsm1-7 or the miRNA-related protein GW182 to form the PB. Later on, they assemble the decapping and degradation enzymes and/or the proteins required for silencing and storage into PB. All the intermediate steps of this process can represent different populations of granules coexisting in the cell and visible with different morphology that might reflect a variety of components and/or diverse stoichiometry.
Mentions: From the previous analysis, one can establish many unsolved aspects on cytoplasmic foci function. One of them is the dynamic of the mRNP remodeling. The current model suggests an active movement of mRNPs from and to polysomes and from and to SG and PB [33]. However, how does it happen and the factors involved are not known. Translationally active mRNAs can interact, in response to errors in translational initiation or to specific recruitment of regulatory proteins, with translational repressors such as Dhh1, Pat 1, Lsm1-7, eIF4E-T. Those factors would promote the replacement of the translational machinery from the mRNA, promote the cap removal and determine degradation [33] or the accumulation of silenced mRNA in PB. Within PB, mRNPs could undergo further remodeling and define a path to follow, including their return to polysomes. In addition, PBs have been shown to interact and exchange components or their own nature with SG (reviewed in [6, 7]) in a process that may result in mRNPs intermediates of unknown nature. Evidence for the diversity of cytoplasmic foci and their components results from immunocytochemistry and colocalization studies. A common factor present in most cytoplasmic mRNPs is the cap-binding protein eIF4E. eIF4E occurs in active polysomes as a translation initiation factor, in SG as part of the stalled initiation complex, and in PB as the only translation factor present there in multicellular eukaryotes. We observed in Drosophila S2 cells that eIF4E colocalizes with different pairs of markers, either for PB (GW182, Lsm1, Me31B—an ortholog of the helicase rck/p54) or SG (TIA-1) and that the colocalization does not occur in all foci in the same way (PVF, CL, and RRP, unpublished data and Figure 1). In some cases, the foci contain one, the other, or both components. In the foci that show colocalization of both factors, the relative amount of each component may vary from foci to foci, as judged by confocal microscopy quantification of the colocalized factors (PVF, CL, RRP, unpublished observation). This implies that there are a diversity of granules. An appealing hypothesis is that eIF4E is a common link among different mRNPs, playing different roles depending on their interactors. One plausible function could be that the accumulation of mRNPs in eIF4E-containing foci is a way to regulate the rate of translation in different physiological states (cell cycle phases, developmental stages, circadian rhythms). Moreover, it has been reported that, in mammalian cells, eIF4E interacts in PB with at least two factors, rck/p54 and eIF4E-T [21]. These are simultaneous interactions within the PB and imply that both proteins could contact different domains of the same eIF4E molecule or that they would represent different populations of mRNPs or different functions within the same PB. In either cases, the complexity of the interactions in vivo is more diverse than it has been expected. A model for the remodeling of active mRNPs to silence and degradation based on Andrei et al. [21] is depicted in Figure 2. This might require several intermediate states that can be the maturation steps of a mRNA in the way of a PB or within a PB. This would correlate with the large diversity of components and interactions within a cytoplasmic foci and the diversity of the foci within a cell. The understanding of the dynamics of mRNP is far from clear and unpredictable paths remain to be discovered. They will need further research and more sophisticated methods for in vivo studies.

Bottom Line: They involve the regulation of the metabolism of mRNA in cytoplasmic foci.A challenging prospective is to know how many different classes of foci exist, which functions they support, how are they formed, and how do they relate one to each other.Here, we present an update of the component of the different granules, a possible function, and hypothesis on their in vivo dynamics related to translational control.

View Article: PubMed Central - PubMed

Affiliation: Centro Regional de Estudios Genómicos, Universidad Nacional de La Plata, CP 1888 Florencio Varela, Argentina.

ABSTRACT
The life of an mRNA from transcription to degradation offers multiple control check points that regulate gene expression. Transcription, splicing, and translation have been widely studied for many years; however, in recent years, new layers of posttranscriptional and posttranslational control have been uncovered. They involve the regulation of the metabolism of mRNA in cytoplasmic foci. They are collections of ribonucleoprotein complexes that, in most cases, remain still uncharacterized, except the processing bodies (PBs) and stress granules (SGs), which have been studied (and reviewed) in detail. A challenging prospective is to know how many different classes of foci exist, which functions they support, how are they formed, and how do they relate one to each other. Here, we present an update of the component of the different granules, a possible function, and hypothesis on their in vivo dynamics related to translational control.

No MeSH data available.